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1、修改阻断孤啡肽受体对大鼠局灶性脑缺血损伤的保护作用王高翔刘文博孙绪德姚立农柴伟摘要目的研究侧脑室给予孤啡肽受体阻断剂对大鼠脑缺血再灌注损伤的影响。方法雄性SD大鼠55只,随机分为假手术组(S组)、对照组(C组)和三个不同剂量的给药组(T0.03、T0.3、T3)。对照组和给药组都采用线栓法阻断大脑中动脉模型(MCAO),缺血2h后恢复再灌注。给药组分别于手术前45min右侧脑室给予孤啡肽受体阻断剂Nphe0.03nmol、0.3nmol、3nmol,体积10ul。S组和C组于手术前相同时间点侧脑室给予相
2、同体积的生理盐水,其中S组给予与C组相同的手术操作但不置于尼龙线。每组大鼠随机分为两部分,其中8只在恢复再灌后24h行行为学评分,后断头取脑行TTC染色,计算脑梗死容积。3只在恢复再灌后24小时断头分离右侧海马组织,WesternBlot法分析caspase-3蛋白表达。结果与C组相比,T0.3和T3给药组的行为评分明显提高,T3组有显著性差异(P<0.05)。T0.3、T3给药组的脑梗死容积明显减小,并有统计学差异(P<0.05)。WesternBlot分析结果显示T0.3、T3组在缺血再灌后24小时
3、caspase-3蛋白表达明显降低。结论阻断孤啡肽受体能剂量依赖性减轻脑缺血再灌注损伤,其机制可能与阻断神经元凋亡有关。[关键词]孤啡肽;孤啡肽受体;脑缺血再灌注;caspase-3TheprotectionoforphaninreceptorantagonistNphe1onfocalcerebralischemiainratsWanggao-xiang,1Liuwen-bo2,Sunxu-de1,Yaoli-long1,Chaiwei11,DepartmentofAnesthesia,theFour
4、thMilitaryMedicalUniversity,Tangduhospital.7100382,DepartmentofNurosurgey,theFourthMilitaryMedicalUniversity,Xijinghospital710032Abstract:ObjectiveToinvestigatetheeffectofintracerebroventricularadministrationofORL-1antaonistoncerebralischemia-reperfusion
5、injuryinrats.MethodsFifty-fivemaleSDratsweredividedrandomlyinto5groups:shamoperatedgroup(Sgroup);controlgroup(Cgroup);treatment0.03nmolgroup(T0.03);treatment0.3nmolgroup(T0.3)andtreatment3nmolgroup(T3).Theanimalsincontrolgroupandtreatmentgroupswereexpose
6、dtothesuturemiddlecerebralarteryocclusion(MCAO)modelandthereperfusionafter2hoursocclusion.TheanimalsintreatmentgroupswereintracerebroventricularlygivenORL-1antagonist(Nphe)45minutesbeforeMCAOsurgery,respectively.TheanimalsinShamandControlgroupsweregivent
7、hesamevolumeofnormalsalineatthesamepoint,ShamandControlgroupsweregiventhesamesetofsurgicaloperation,butnot作者单位:710038西安市,第四军医大学唐都医院麻醉科(王高翔、孙绪德,、姚立农、柴伟);第四军医大学神经外科(刘文博)责任作者柴伟placedinnylonline.Alltheanimalsineachgroupwererandomlydividedintotwoparts:eightof
8、themforbehavioralscoreandTTCstainingat24hoursafterMCAOsurgery;threeofthemfordetectingcaspase-3levelinrighthippocampusbyWestern-blotat24hoursafterMCAOsurgery.ResultsComparedwiththecontrolgroup,thebehaviorscoresinT0.3andT3gr